Recent clinical trials evaluating the combination of chemotherapy with immune checkpoint inhibition for the primary treatment of lung cancer showed increased progression-free and overall survival compared with chemotherapy alone. However, the combination of these two modalities is less than additive and the mechanisms of resistance to this therapeutic intervention are discussed here. So far, the conventional biomarkers for immunotherapy, namely programmed death-ligand 1 expression or tumor mutational burden are poor predictors of the efficacy of immunochemotherapy, and the optimal sequence of chemotherapy and immunotherapy has yet to be defined